Urinary concentrations of 3-(diethylcarbamoyl)benzoic acid (DCBA), a major metabolite of N,N-diethyl-m-toluamide (DEET) and semen parameters among men attending a fertility center.

STUDY QUESTION: Are specific gravity (SG)-adjusted urinary concentrations of 3-(diethylcarbamoyl)benzoic acid (DCBA) associated with semen parameters among men attending an academic fertility center? SUMMARY ANSWER: Our study did not demonstrate any association between SG-adjusted urinary DCBA concentrations and semen parameters among men attending an academic fertility center. WHAT IS KNOWN ALREADY: N,N-Diethyl-m-toluamide (DEET) is the most common active ingredient in consumer insect repellents. The recent rise in public health concerns regarding mosquito-borne diseases such as Zika, have led to an increased use of DEET insect repellents, especially among couples planning pregnancy. Animal studies have observed reproductive toxicity from DEET exposure. However, the reproductive health effects of DEET and its metabolites on human reproduction are unknown. STUDY DESIGN, SIZE, DURATION: Between 2007 and 2015, 90 men participating in a prospective cohort study at the Massachusetts General Hospital Fertility Center provided 171 urine samples and 250 semen samples for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: The urinary concentrations of DEET, N,N-diethyl-3-hydroxymethylbenzamide (DHMB) and DCBA were quantified by isotope-dilution tandem mass spectrometry and adjusted by SG. We used linear mixed models to evaluate the association between tertiles of SG-adjusted urinary DCBA concentrations and semen parameters (semen volume, sperm concentration, total sperm count, progressive motility, total progressive motility count, normal morphology and total normal morphology count), adjusting for covariates. DEET and DHMB were not considered for analysis because of the low percentage of detectable concentrations (<7%). Effect modification by BMI and smoking status was explored. MAIN RESULTS AND THE ROLE OF CHANCE: Participants had a median age of 36 years and BMI of 27 kg/m2, and 68% had never smoked. The SG-adjusted geometric mean DCBA urinary concentration was 2.20 µg/l, with 85% detection frequency. The majority of semen parameters fell within the normal range with the exception of progressive motility, where 64% of the men had values below the WHO 2010 lower reference limits. SG-adjusted urinary DCBA concentrations were not associated with semen parameters in unadjusted or adjusted models. Men in the highest tertile of SG-adjusted urinary DCBA concentrations had comparable semen parameters to men in the lowest tertile (2.59 vs. 2.88 ml for semen volume, 47.9 vs. 45.8 million/ml for sperm concentration, 116 vs. 118 million for total sperm count, 25 vs. 24% for progressive sperm motility, and 6.1 vs. 5.8% for morphologically normal sperm). In addition, BMI and smoking status did not modify the associations. LIMITATIONS REASONS FOR CAUTION: We had a relatively small sample size with similar socioeconomic backgrounds and with overall relatively low urinary concentrations of DEET biomarkers. However, our sample size was enough to detect moderate differences with at least 80% statistical power, between the first and third tertiles of urinary DCBA concentrations. Limitations also include possible misclassification of DCBA exposure and difficulties in extrapolating the findings to the general population. WIDER IMPLICATIONS OF THE FINDINGS: Our study found no associations between urinary concentrations of DCBA, a major metabolite of the insect repellent DEET, and semen parameters in men presenting for infertility treatment. While these results are reassuring, further studies including larger sample sizes and higher exposures are warranted. STUDY FUNDING/COMPETING INTEREST(S): The project was financed by the National Institute of Health grants R01ES022955 and R01ES009718 and by grant P30ES000002 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. TRIAL REGISTRATION NUMBER: N/A.

Association of N, N-diethyl-m-toluamide (DEET) with hyperuricemia among adult participants.

BACKGROUND: N,N-diethyl-m-toluamide (DEET) is a widely used active ingredient in insect repellents, and its effects on human health have been a matter of debate. This study aims to investigate the relationship between DEET exposure and hyperuricemia in the adult population. METHODS: Our study utilized a cross-sectional design and analyzed data from adult participants of the National Health and Nutrition Examination Survey (NHANES) conducted between 2007 and 2016. 3-diethyl-carbamoyl benzoic acid (DCBA) was used as a specific indicator of DEET exposure. DCBA was categorized using quartiles based on its distribution within the study population. Multiple linear regression models were employed to examine the association between DCBA exposure and serum uric acid (SUA) levels in adults. The relationship between DCBA and the prevalence of hyperuricemia in adults was assessed using multiple logistic regression models. Dose-response relationships were analyzed using restricted cubic spline regression. RESULTS: A total of 8708 participants were included in the study. The mean age of the participants was 46.49 years, and the total number of male participants was 50.93%. The median levels of DCBA and SUA were 2.07 ng/mL and 5.40 mg/dL, respectively. Hyperuricemia was found in 19.99% of the participants. In multivariate-adjusted linear regression models, it was found that higher SUA levels were associated with the highest quartile of DCBA compared with the lowest quartile of DCBA (ß [95% CI]: 0.19 [0.08, 0.30], Ptrend<0.001). After adjusting for confounders, a positive association was found between the prevalence of hyperuricemia and DCBA levels (OR [95% CI] quartile 4 vs. 1: 1.41 [1.14-1.74], Ptrend<0.001). Furthermore, linear associations were observed between DCBA concentrations and SUA levels (P for nonlinearity = 0.479) and the prevalence of hyperuricemia (P for nonlinearity = 0.755). CONCLUSION: Higher DCBA concentrations were found to have a positive association with the prevalence of hyperuricemia in the general adult population.

Biomonitoring of DEET and DCBA in Canadian children following typical protective insect repellent use.

N,N-diethyl-m-toluamide (DEET) is an ingredient found in many consumer insect repellents and its use is recommended to Canadians by government agencies, including Health Canada, for protection against insect bites including mosquitos and ticks. The majority of research on DEET exposure and toxicokinetics in humans has focused on adult populations with little information from vulnerable populations, including children. We aimed to fill this knowledge gap by examining real-world exposure data for DEET and its metabolite 3-diethylcarbamoyl benzoic acid (DCBA) in a sample population of Canadian children. We conducted a 24-h observational exposure human biomonitoring study at three overnight summer camps in Ontario, Canada through July and August 2019. Participating children aged 7-13 years provided multiple spot urine samples over a 24-h period and completed a journal to document insect repellent use and factors that could influence absorption of DEET. Children were instructed to use insect repellent as they usually would while attending a summer camp. Exposure was quantified using the information from the participant's journal and the change in the mass of their insect repellent containers over the course of the study. A total of 389 urine samples were collected from 124 children. Among participants using insect repellent, urinary levels of DEET were elevated between 2 and 8 h post-application and decreased thereafter but remained qualitatively higher than concentrations in participants who did not use insect repellent on the study day, even at 18-22 h post-application. DCBA was the predominant metabolite of DEET exposure in urine. DCBA was elevated between 8 and 14 h post-application, and declined thereafter, but not to the level observed among those who did not use insect repellent on the study day. Children who used more insect repellent, or used higher concentration insect repellent (10%-30% DEET) excreted higher levels of DEET and DCBA. Excreted DEET and DCBA accounted for 0.001% (median) and 1.3% (median) of the estimated applied DEET, respectively. Children did not reach an undetectable level of DEET or DCBA in urine, even among those not using insect repellent during the study day, indicating a potentially complex multi-route exposure to insect repellents in a real world scenario. This work provides targeted biomonitoring data for children intentionally using DEET-based insect repellents for normal protective use, and will support the risk re-evaluation of DEET by Health Canada.

Exposure to N,N-diethyl-m-toluamide and cardiovascular diseases in adults.

Although growing evidence suggests that N,N-diethyl-m-toluamide (DEET) has adverse effects on public health, the relationship of DEET with cardiovascular disease (CVD) is still largely unknown. The purpose of this study was, therefore, to evaluate the association between DEET exposure and total and specific CVD among the US adults. In this cross-sectional study, a total of 5,972 participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2007-2014. CVD was defined as a combination of congestive heart failure (CHF), coronary heart disease (CHD), angina, heart attack, or stroke. Logistic regression models were used to evaluate the association between DEET metabolites and the risks of total and specific CVD. Compared to the lowest quartile, 3-(diethylcarbamoyl) benzoic acid (DCBA) in the highest quartile was associated with the increased risks of CVD (odds ratio [OR]: 1.32, 95% CI: 1.03-1.68, P for trend = 0.025) and CHD (OR: 1.57, 95% CI: 1.10-2.25, P for trend = 0.017), after adjustment for potential covariates. Nevertheless, exposure to DCBA was not significantly associated with heart attack, CHF, angina, and stroke. Further studies are required to confirm these findings and identify the underlying mechanisms.